Inclusion Criteria:

- Histologically or cytologically proven metastatic colorectal adenocarcinoma that is
refractory to standard therapy and not amenable to surgery with curative intent.

- Tumor characteristics:

- At least one lesion that is suitable for a repeated biopsy; eg. subcutaneous
nodule, skin lesion, rectal tumor, colonic mass easily reached by colonoscopy,
peritoneal masses at least 3cm in maximum diameter that are easily assessable by
image guided core biopsy.

- For liver lesions, more superficially located lesions at least 3cm in maximum
dimension with a rim of normal liver tissue, assessable safely by image guided
core biopsy as determined by an experienced interventional radiologist.

- Eastern Cooperative Oncology Group ECOG performance status of 0 or 1 (see Appendix
10.4).

- Adequate bone marrow function (absolute neutrophil count =1,500/mm3; platelet count
=100000/mm3; hemoglobin =9g/dl

- Adequate liver and renal function as assessed by the following laboratory
requirements conducted within 7 days of starting to study treatment:

- Total bilirubin < 1.5 x the upper limit of normal (ULN).

- Alanine transaminase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN (< 5
x ULN for patients with liver involvement of their cancer).

- Amylase and lipase < 1.5 x the ULN

- Serum creatinine < 1.5 x the ULN.

- Glomerular filtration rate (GFR) = 30 ml/min/1.73 m2 according to the MDRD
(Modified diet in renal disease) abbreviated formula

- Prothrombin time, international normalized ratio (INR) and partial thromboplastin
time less than or equal to 1.2 times the ULN.

- Male or female at least 21 years of age.

- A female subject is eligible to enter and participate in the study if she is:

- Non-childbearing potential (ie. physiologically incapable of becoming pregnant)
including any women who:

- Has had a hysterectomy or

- Has bilateral oophorectomy (ovariectomy) or

- Has bilateral tubal ligation or

- Is postmenopausal (demonstrate total cessation of menses for greater than or

- Childbearing potential, has a negative serum or urine pregnancy test at
screening, agrees to one of the following: double barrier contraception or
abstinence.

- Predicted life expectancy of at least 12 weeks.

- Resting oxygen saturation greater than 92% on room air.

- Written informed consent.

- Able to swallow and retain oral medication.

- Prothrombin time (PT), International Normalized Ratio for PT (PT INR), and partial
thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) within
normal limits.

Exclusion Criteria: